title: Human immunodeficiency virus-specific gamma interferon enzyme-linked immunospot assay responses targeting specific regions of the proteome during primary subtype C infection are poor predictors of the course of viremia and set point.
abstract: It is unknown whether patterns of human immunodeficiency virus (HIV)-specific T-cell responses during acute infection may influence the viral set point and the course of disease. We wished to establish whether the magnitude and breadth of HIV type 1 (HIV-1)-specific T-cell responses at 3 months postinfection were correlated with the viral-load set point at 12 months and hypothesized that the magnitude and breadth of HIV-specific T-cell responses during primary infection would predict the set point. Gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay responses across the complete proteome were measured in 47 subtype C HIV-1-infected participants at a median of 12 weeks postinfection. When corrected for amino acid length and individuals responding to each region, the order of recognition was as follows: Nef > Gag > Pol > Rev > Vpr > Env > Vpu > Vif > Tat. Nef responses were significantly (P < 0.05) dominant, targeted six epitopic regions, and were unrelated to the course of viremia. There was no significant difference in the magnitude and breadth of responses for each protein region with disease progression, although there was a trend of increased breadth (mean, four to seven pools) in rapid progressors. Correlation of the magnitude and breadth of IFN-gamma responses with the viral set point at 12 months revealed almost zero association for each protein region. Taken together, these data demonstrate that the magnitude and breadth of IFN-gamma ELISPOT assay responses at 3 months postinfection are unrelated to the course of disease in the first year of infection and are not associated with, and have low predictive power for, the viral set point at 12 months.
authors.affiliation: National Institute for Communicable Diseases, Private Bag X4, Johannesburg 2131, South Africa. cgray@nicd.ac.za.
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray
authors.forename: Mandla
authors.initials: M
authors.lastname: Mlotshwa
authors.forename: Catherine
authors.initials: C
authors.lastname: Riou
authors.forename: Tiyani
authors.initials: T
authors.lastname: Mathebula
authors.forename: Debra
authors.initials: D
authors.lastname: de Assis Rosa
authors.forename: Tumelo
authors.initials: T
authors.lastname: Mashishi
authors.forename: Cathal
authors.initials: C
authors.lastname: Seoighe
authors.forename: Nobubelo
authors.initials: N
authors.lastname: Ngandu
authors.forename: Francois
authors.initials: F
authors.lastname: van Loggerenberg
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.forename: Salim Abdool
authors.initials: SA
authors.lastname: Karim
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D014766:Viremia
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; D007371:Interferon-gamma